Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity
Lachke, Salil A.
Bulyk, Martha L.
Maas, Richard L.
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CitationRowan, S., T. Siggers, S. A. Lachke, Y. Yue, M. L. Bulyk, and R. L. Maas. 2010. “Precise Temporal Control of the Eye Regulatory Gene Pax6 via Enhancer-Binding Site Affinity.” Genes & Development 24 (10): 980–85. https://doi.org/10.1101/gad.1890410.
AbstractHow transcription factors interpret the cis-regulatory logic encoded within enhancers to mediate quantitative changes in spatiotemporally restricted expression patterns during animal development is not well understood. Pax6 is a dosage-sensitive gene essential for eye development. Here, we identify the Prep1 (pKnox1) transcription factor as a critical dose-dependent upstream regulator of Pax6 expression during lens formation. We show that Prep1 activates the Pax6 lens enhancer by binding to two phylogenetically conserved lower-affinity DNA-binding sites. Finally, we describe a mechanism whereby Pax6 levels are determined by transcriptional synergy of Prep1 bound to the two sites, while timing of enhancer activation is determined by binding site affinity.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41482936
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